Pizzulli L, Zirbes M, Hagendorff A, Kattenbeck K, Lüderitz B
Medizinische Universitätsklinik und Poliklinik, Bonn.
Z Kardiol. 1996 Nov;85(11):847-55.
It is still a matter of dispute to what extent a direct loss of nitrate mediated vasodilatation (true tolerance) contributes to the development of nitrate tolerance. Aim of this study was to assess to what extent the dilatation of non-obstructed segments of epicardial arteries is attenuated during a continuous 24- and 48-h-infusion of nitroglycerin. In a prospective, randomized and blinded study we investigated 32 patients who underwent diagnostic coronary angiography. All cardiac medication was withdrawn at least for 24 h; patients were randomized to either a 24 h NTG-infusion (group A; 0-24 h saline infusion followed by a 24 h NTG-infusion; n = 16) or a 48 h NTG-infusion (group B; 0-48 h of NTG-infusion; n = 16) in a dosage of 1.5 micrograms/ kg/min. The patients were included if 5 proximal segments of the left coronary artery showed no visible atherosclerosis. A coronary angiography was performed after 24 and 48 h respectively. The lumen diameters were measured by quantitative coronary analysis at baseline and 1 and 3 min after application of 0.2 mg of NTG intracoronarially (i.c.). Blood samples were drawn before and after 24 and 48 h of infusions to measure hematocrit and neurohormones. In group A after 24 h of saline infusion there was a significant increase in lumen diameter from 3.14 +/- 0.17 mm at baseline to 3.51 +/- 0.11 mm (p < 0.001) and 3.60 +/- 0.21 mm (p < 0.001) after 1 and 3 min of NTG i.e. respectively. After 24 h of NTG-infusion there were no significant changes in baseline and values after further NTG i.e. In group B after 24 h of NTG-infusion no significant change in lumen diameter was detectable after NTG i.e. (3.57 +/- 0.23 mm to 3.63 +/- 0.13 mm) and the mean diameter remained unchanged after prolongation of NTG to 48 h (3.58 +/- 0.33 mm). There were no significant differences between the baseline values and the responses to i.e. NTG after 24 and 48 h of NTG infusion. Hematocrit and aldosterone levels decreased significantly after NTG-infusion but not following saline. Renin and norepinephrine remained unchanged throughout the NTG-infusion-periods.
The vasodilatation of non-obstructed segments of epicardial arteries persists during a prolonged infusion period and there is no induction of vascular tolerance between the 24 and 48 h infusion period. These findings further support that there is a different susceptibility of arteries and veins to nitrate tolerance.
